tbuckley/cabot-search huggingface dataset:
Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non–Small-Cell Lung Cancer (NADIM phase II trial)
Authors: Mariano Provencio, Roberto Serna-Blasco, Ernest Nadal, Amelia Insa, M. Rosario García-Campelo, Joaquín Casal Rubio, Manuel Dómine, Margarita Majem, Delvys Rodríguez-Abreu, Alex Martínez-Martí, Javier De Castro Carpeño, Manuel Cobo, Guillermo López Vivanco, Edel Del Barco, Reyes Bernabé Caro, Nuria Viñolas, Isidoro Barneto Aranda, Santiago Viteri, Eva Pereira, Ana Royuela, Virginia Calvo, Javier Martín-López, Francisco García-García, Marta Casarrubios, Fernando Franco, Estela Sánchez-Herrero, Bartomeu Massuti, Alberto Cruz-Bermúdez, Atocha Romero
Journal: Journal of Clinical Oncology (2022)

Neoadjuvant chemotherapy plus nivolumab has been shown to be effective in resectable non-small-cell lung cancer (NSCLC) in the NADIM trial (ClinicalTrials.gov identifier: NCT03081689). The 3-year overall survival (OS) and circulating tumor DNA (ctDNA) analysis have not been reported.This was an open-label, multicenter, single-arm, phase II trial in which patients with stage IIIA NSCLC, who were deemed to be surgically resectable, were treated with neoadjuvant paclitaxel (200 mg/m2 once a day) and carboplatin (area under curve 6) plus nivolumab (360 mg) once on day 1 of each 21-day cycle, for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The 3-year OS and ctDNA analysis were secondary objectives of the trial.OS at 36 months was 81.9% (95% CI, 66.8 to 90.6) in the intention-to-treat population, rising to 91.0% (95% CI, 74.2 to 97.0) in the per-protocol population. Neither tumor mutation burden nor programmed cell death ligand-1 staining was predictive of survival. Conversely, low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and OS (hazard ratio [HR], 0.20; 95% CI, 0.06 to 0.63, and HR, 0.07; 95% CI, 0.01 to 0.39, respectively). Clinical responses according to RECIST v1.1 criteria did not predict survival outcomes. However, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and OS (HR, 0.26; 95% CI, 0.07 to 0.93, and HR, 0.04; 95% CI, 0.00 to 0.55, respectively). The C-index to predict OS for ctDNA levels after neoadjuvant treatment (0.82) was superior to that of RECIST criteria (0.72).The efficacy of neoadjuvant chemotherapy plus nivolumab in resectable NSCLC is supported by 3-year OS. ctDNA levels were significantly associated with OS and outperformed radiologic assessments in the prediction of survival.
Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study
Authors: Byoung Chul Cho, Delvys Rodriguez Abreu, Maen Hussein, Manuel Cobo, Anjan J Patel, Nevena Secen, Ki Hyeong Lee, Bartomeu Massuti, Sandrine Hiret, James Chih Hsin Yang, Fabrice Barlesi, Dae Ho Lee, Luis Paz Ares, Robert W Hsieh, Namrata S Patil, Patrick Twomey, Xiaoying Yang, Raymond Meng, Melissa L Johnson
Journal: The Lancet Oncology (2022)
EULAR 75-year anniversary: commentaries on key ARD papers from 1947
Authors: Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2022)

EULAR is celebrating its 75-year anniversary after the foundation in 1947.ARD is contributing to this celebration by presenting a series of previously published articles that highlight the development of rheumatology over these 75 years.Comments to the first four selected papers published in 1947 appear in this issue.Importantly, one of these papers presents a brief report from the first European congress of rheumatology, held in Copenhagen in 1947.It is, therefore, also important that the anniversary congress in 2022 is organised in the same city.The foundation of EULAR in 1947 is also described in the introduction to this report.At that time, the International League against Rheumatism (ILAR) was the global umbrella organisation and a European section was formed 'on the same lines as the Pan-American section established during the war'.Later, ILAR also included the Asian and Pacific League against Rheumatism and the African League.ILAR organised separate international congresses, the last in Edmonton in 2001, and its organisation, role and by-laws were changed around 2006.Today, each of these four 'leagues' is organising their own congress, in addition to the congress organised by the American College of Rheumatology (ACR).The congress report illustrates that the rheumatologists also at that time had a broad focus on musculoskeletal diseases, even if some topics will not be recognised as important by younger rheumatologists today, for example, antistreptolysin antibodies.It is also mentioned that a full session addressed treatment of rheumatoid arthritis (RA) by gold salts and chemotherapy, and that 'new work reported by Svartz (Sweden) on treatment of arthritis with sulphonamides still awaits confirmation'.Professor Nanna Svartz developed sulphasalazine, which is still used in the treatment of RA and of spondyoloarthritis with peripheral joint involvement.George D. Steven published another interesting paper in 1947 with the title 'X-ray appearances in chronic rheumatism'. 1 The main focus of this paper was RA, osteoarthritis (OA) and gout.Many of the imaging findings that we also focus on today are described, like cartilage loss and bone erosions in RA.However, the opportunity for using scoring systems for evaluation of radiographic progression is not mentioned, which is perhaps not surprising since the scoring systems in RA and OA first were published in the 1971 and in 1957, respectively. 2 3 This paper also includes a section called 'Differential Features in Other Diseases'.The first part of this section focuses on ankylosing spondylitis (AS), but very briefly.My interpretation is that AS was
Nonalcoholic fatty liver disease risk and histologic severity are associated with genetic polymorphisms in children
Authors: Nidhi P. Goyal, Sara B. Rosenthal, Chanod Nasamran, Cynthia A. Behling, Jorge E. Angeles, Mark H. Fishbein, Kathryn E. Harlow, Ajay K. Jain, Jean P. Molleston, Kimberly P. Newton, Patricia Ugalde‐Nicalo, Stavra A. Xanthankos, Katherine Yates, Nicholas J. Schork, Kathleen M. Fisch, Jeffrey B. Schwimmer
Journal: Hepatology (2022)

Background and Aims: NAFLD is the most common chronic liver disease in children. Large pediatric studies identifying single nucleotide polymorphisms (SNPs) associated with risk and histologic severity of NAFLD are limited. Study aims included investigating SNPs associated with risk for NAFLD using family trios and association of candidate alleles with histologic severity. Approach and Results: Children with biopsy‐confirmed NAFLD were enrolled from the NASH Clinical Research Network. The Expert Pathology Committee reviewed liver histology. Genotyping was conducted with allele‐specific primers for 60 candidate SNPs. Parents were enrolled for trio analysis. To assess risk for NAFLD, the transmission disequilibrium test was conducted in trios. Among cases, regression analysis assessed associations with histologic severity. A total of 822 children with NAFLD had mean age 13.2 years (SD 2.7) and mean ALT 101 U/L (SD 90). PNPLA3 (rs738409) demonstrated the strongest risk ( p = 2.24 × 10 −14 ) for NAFLD. Among children with NAFLD, stratifying by PNPLA3 s738409 genotype, the variant genotype associated with steatosis ( p = 0.005), lobular ( p = 0.03) and portal inflammation ( p = 0.002). Steatosis grade associated with TM6SF2 ( p = 0.0009), GCKR ( p = 0.0032), PNPLA3 rs738409 ( p = 0.0053), and MTTP ( p = 0.0051). Fibrosis stage associated with PARVB rs6006473 ( p = 0.0001), NR1I2 ( p = 0.0021), ADIPOR2 ( p = 0.0038), and OXTR ( p = 0.0065). PNPLA3 rs738409 ( p = 0.0002) associated with borderline zone 1 NASH. Conclusions: This study demonstrated disease‐associated SNPs in children with NAFLD. In particular, rs6006473 was highly associated with severity of fibrosis. These hypothesis‐generating results support future mechanistic studies of development of adverse outcomes such as fibrosis and generation of therapeutic targets for NAFLD in children.
Hepatocellular cystathionine γ lyase/hydrogen sulfide attenuates nonalcoholic fatty liver disease by activating farnesoid X receptor
Authors: Wenjing Xu, Changting Cui, Chunmei Cui, Zhenzhen Chen, Haizeng Zhang, Qinghua Cui, Guoheng Xu, Jianglin Fan, Yu Han, Liangjie Tang, Giovanni Targher, Christopher D. Byrne, Ming‐Hua Zheng, Liming Yang, Jun Cai, Bin Geng
Journal: Hepatology (2022)

Hydrogen sulfide (H2 S) plays a protective role in NAFLD. However, whether cystathionine γ lyase (CSE), a dominant H2 S generating enzyme in hepatocytes, has a role in the pathogenesis of NAFLD is currently unclear.We showed that CSE protein expression is dramatically downregulated, especially in fibrotic areas, in livers from patients with NAFLD. In high-fat diet (HFD)-induced NAFLD mice or an oleic acid-induced hepatocyte model, the CSE/H2 S pathway is also downregulated. To illustrate a regulatory role for CSE in NAFLD, we generated a hepatocyte-specific CSE knockout mouse (CSELKO ). Feeding an HFD to CSELKO mice, they showed more hepatic lipid deposition with increased activity of the fatty acid de novo synthesis pathway, increased hepatic insulin resistance, and higher hepatic gluconeogenic ability compared to CSELoxp control mice. By contrast, H2 S donor treatment attenuated these phenotypes. Furthermore, the protection conferred by H2 S was blocked by farnesoid X receptor (FXR) knockdown. Consistently, serum deoxycholic acid and lithocholic acid (FXR antagonists) were increased, and tauro-β-muricholic acid (FXR activation elevated) was reduced in CSELKO . CSE/H2 S promoted a post-translation modification (sulfhydration) of FXR at Cys138/141 sites, thereby enhancing its activity to modulate expression of target genes related to lipid and glucose metabolism, inflammation, and fibrosis. Sulfhydration proteomics in patients' livers supported the CSE/H2 S modulation noted in the CSELKO mice.FXR sulfhydration is a post-translational modification affected by hepatic endogenous CSE/H2 S that may promote FXR activity and attenuate NAFLD. Hepatic CSE deficiency promotes development of nonalcoholic steatohepatitis. The interaction between H2 S and FXR may be amenable to therapeutic drug treatment in NAFLD.
Genomic Shifts, Phenotypic Clines, and Fitness Costs Associated With Cold Tolerance in the Asian Tiger Mosquito
Authors: Stéphanie Sherpa, Jordan Tutagata, Thierry Gaude, Frédéric Laporte, Shinji Kasai, Intan H. Ishak, Xiang Guo, Jiyeong Shin, Sébastien Boyer, Sébastien Marcombe, Theeraphap Chareonviriyaphap, Jean-Philippe David, Xiao-Guang Chen, Xiaohong Zhou, Laurence Després
Journal: Molecular Biology and Evolution (2022)

Abstract Climatic variation is a key driver of genetic differentiation and phenotypic traits evolution, and local adaptation to temperature is expected in widespread species. We investigated phenotypic and genomic changes in the native range of the Asian tiger mosquito, Aedes albopictus. We first refine the phylogeographic structure based on genome-wide regions (1,901 double-digest restriction-site associated DNA single nucleotide polymophisms [ddRAD SNPs]) from 41 populations. We then explore the patterns of cold adaptation using phenotypic traits measured in common garden (wing size and cold tolerance) and genotype–temperature associations at targeted candidate regions (51,706 exon-capture SNPs) from nine populations. We confirm the existence of three evolutionary lineages including clades A (Malaysia, Thailand, Cambodia, and Laos), B (China and Okinawa), and C (South Korea and Japan). We identified temperature-associated differentiation in 15 out of 221 candidate regions but none in ddRAD regions, supporting the role of directional selection in detected genes. These include genes involved in lipid metabolism and a circadian clock gene. Most outlier SNPs are differently fixed between clades A and C, whereas clade B has an intermediate pattern. Females are larger at higher latitude yet produce no more eggs, which might favor the storage of energetic reserves in colder climate. Nondiapausing eggs from temperate populations survive better to cold exposure than those from tropical populations, suggesting they are protected from freezing damages but this cold tolerance has a fitness cost in terms of egg viability. Altogether, our results provide strong evidence for the thermal adaptation of A. albopictus across its wide temperature range.
WHO Program May Eliminate Active Trachoma’s Blindness Risk by 2030
Authors: Howard D. Larkin
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Canine ACL reconstruction with an injectable hydroxyapatite/collagen paste for accelerated healing of tendon-bone interface
Authors: Qingsong Jiang, Liren Wang, Zhanhong Liu, Jinlei Su, Yajun Tang, Peijie Tan, Xiangdong Zhu, Kai Zhang, Xing Ma, Jia Jiang, Jinzhong Zhao, Hai Lin, Xingdong Zhang
Journal: Bioactive Materials (2022)

Healing of an anterior cruciate ligament (ACL) autologous graft in a bone tunnel occurs through the formation of fibrovascular scar tissue, which is structurally and compositionally inferior to normal fibrocartilaginous insertion and thus may increase the reconstruction failure and the rate of failure recurrence. In this study, an injectable hydroxyapatite/type I collagen (HAp/Col Ⅰ) paste was developed to construct a suitable local microenvironment to accelerate the healing of bone-tendon interface. Physicochemical characterization demonstrated that the HAp/Col Ⅰ paste was injectable, uniform and stable. The in vitro cell culture illustrated that the paste could promote MC3T3-E1 cells proliferation and osteogenic expression. The results of a canine ACL reconstruction study showed that the reconstructive ACL had similar texture and color as the native ACL. The average width of the tunnel, total bone volume, bone volume/tissue volume and trabecular number acquired from micro-CT analysis suggested that the healing of tendon-bone interface in experimental group was better than that in control group. The biomechanical test showed the maximal loads in experimental group achieved approximately half of native ACL's maximal load at 24 weeks. According to histological examination, Sharpey fibers could be observed as early as 12 weeks postoperatively while a typical four-layer transitional structure of insertion site was regenerated at 48 weeks in the experimental group. The injectable HAp/Col Ⅰ paste provided a biomimetic scaffold and microenvironment for early cell attachment and proliferation, further osteogenic expression and extracellular matrix deposition, and in vivo structural and functional regeneration of the tendon-bone interface.
Incidence, mortality, risk factors, and trends for Hodgkin lymphoma: a global data analysis
Authors: Junjie Huang, Wing Sze Pang, Veeleah Lok, Lin Zhang, Don Eliseo Lucero-Prisno, Wanghong Xu, Zhi-Jie Zheng, Edmar Elcarte, Mellissa Withers, Martin C. S. Wong
Journal: Journal of Hematology & Oncology (2022)

Hodgkin lymphoma is a lymphatic malignancy commonly found in cervical lymph nodes. This study evaluated the worldwide incidence, mortality, associated risk factors, and temporal trends of Hodgkin lymphoma by sex, age, and country.The age-standardised Hodgkin lymphoma incidence and mortality were retrieved from the GLOBOCAN, CI5 volumes I-XI, WHO mortality database, the NORDCAN and SEER Program. The age-standardised prevalence of smoking, alcohol drinking, obesity, and hypertension was also extracted for each country. Trends were tested using Average Annual Percentage Change (AAPC) from Joinpoint regression analysis.The Hodgkin lymphoma incidence and mortality were 0.98 and 0.26 per 100,000 in 2020. A higher incidence was observed in high-income countries, while higher mortality was found in low-income countries. Incidence and mortality were associated with GDP per capita, prevalence of smoking, obesity, and hypertension at the population level. Despite the decreasing mortality trend, there was an increasing incidence, especially among females, younger population, and subjects from Asian countries.There was an increasing trend in Hodgkin lymphoma incidence, especially among subjects who were female, younger population, and from Asian countries. Further studies are needed to investigate the reasons for these epidemiologic trends.
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Authors: Daniel Whiting, John Geddes, Seena Fazel
Journal: JAMA Psychiatry (2022)

Kristina M. Deligiannidis, MD; Samantha Meltzer-Brody, MD, MPH; Handan Gunduz-Bruce, MD, MBA; James Doherty, PhD; Jeffrey Jonas, MD; Sigui Li, MS; Abdul J. Sankoh, PhD; Christopher Silber, MD; Andrew D. Campbell, PhD; Brian Werneburg, PhD; Stephen J. Kanes, MD, PhD; Robert Lasser, MD, MBA
Long term impact of prophylactic antibiotic use before incision versus after cord clamping on children born by caesarean section: longitudinal study of UK electronic health records
Authors: Dana Šumilo, Krishnarajah Nirantharakumar, Brian H Willis, Gavin M Rudge, James Martin, Krishna Gokhale, Rasiah Thayakaran, Nicola J Adderley, Joht Singh Chandan, Kelvin Okoth, Isobel M Harris, Ruth Hewston, Magdalena Skrybant, Jonathan J Deeks, Peter Brocklehurst
Journal: BMJ (2022)

Abstract Objective To investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping. Design Observational controlled interrupted time series study. Setting UK primary and secondary care. Participants 515 945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement Network and Clinical Practice Research Datalink), and 7 147 884 children with linked maternal records in the Hospital Episode Statistics database covering England, of which 3 945 351 were linked to hospitals that reported the year of policy change to administer prophylactic antibiotics for caesarean section before incision rather than after cord clamping. Intervention Fetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure. Main outcome measures The primary outcomes were incidence rate ratios of asthma and eczema in children born by caesarean section when pre-incision prophylactic antibiotics were recommended compared with those born when antibiotics were administered post-cord clamping, adjusted for temporal changes in the incidence rates in children born vaginally. Results Prophylactic antibiotics administered before incision for caesarean section compared with after cord clamping were not associated with a significantly higher risk of asthma (incidence rate ratio 0.91, 95% confidence interval 0.78 to 1.05) or eczema (0.98, 0.94 to 1.03), including asthma and eczema resulting in hospital admission (1.05, 0.99 to 1.11 and 0.96, 0.71 to 1.29, respectively), up to age 5 years. Conclusions This study found no evidence of an association between pre-incision prophylactic antibiotic use and risk of asthma and eczema in early childhood in children born by caesarean section.
Abstract IA004: Tracking population heterogeneity and chemoresistance with functionalized cell barcodes
Authors: Amy Brock
Journal: Cancer Research (2022)

Abstract Heterogeneity across individual cancer cells and clonal populations impacts growth rate, tumor composition, and response to therapy. To improve treatment, new tools are required to measure and control the contributions of diverse cell subpopulations. Our team has developed a high-complexity expressed barcode system, ClonMapper, that integrates expressed cell barcoding with single-cell RNA-sequencing and clonal isolation to characterize and track subpopulation trajectories. Using this approach, we uncovered subsets of cells from cell models with distinct transcriptional signatures and chemotherapy survivorship trajectories. To gain a deeper understanding of the process of clonal diversification, we profiled clones and retrieved sub-clones over the course of expansion and treatment. Supervised learning indicated that clonal subpopulations have characteristic transcriptomic signatures that are well-conserved under a variety of therapeutic perturbations. By providing the capability for systematic dissection of complex clonal dynamics, ClonMapper enables the delineation of an underlying engine of clonal diversification in cancer cell populations and refines our understanding of clonal identity. Citation Format: Amy Brock. Tracking population heterogeneity and chemoresistance with functionalized cell barcodes [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA004.
The Lancet Psychiatry Commission on intimate partner violence and mental health: advancing mental health services, research, and policy
Authors: Sian Oram, Helen L Fisher, Helen Minnis, Soraya Seedat, Sylvia Walby, Kelsey Hegarty, Khadj Rouf, Caroline Angénieux, Felicity Callard, Prabha S Chandra, Seena Fazel, Claudia Garcia-Moreno, Marion Henderson, Emma Howarth, Harriet L MacMillan, Laura K Murray, Sajaratulnisah Othman, Dan Robotham, Marta B Rondon, Angela Sweeney, Danny Taggart, Louise M Howard
Journal: The Lancet Psychiatry (2022)
Identifying who has long COVID in the USA: a machine learning approach using N3C data
Authors: Emily R Pfaff, Andrew T Girvin, Tellen D Bennett, Abhishek Bhatia, Ian M Brooks, Rachel R Deer, Jonathan P Dekermanjian, Sarah Elizabeth Jolley, Michael G Kahn, Kristin Kostka, Julie A McMurry, Richard Moffitt, Anita Walden, Christopher G Chute, Melissa A Haendel, Carolyn Bramante, David Dorr, Michele Morris, Ann M Parker, Hythem Sidky, Ken Gersing, Stephanie Hong, Emily Niehaus
Journal: The Lancet Digital Health (2022)

Post-acute sequelae of SARS-CoV-2 infection, known as long COVID, have severely affected recovery from the COVID-19 pandemic for patients and society alike. Long COVID is characterised by evolving, heterogeneous symptoms, making it challenging to derive an unambiguous definition. Studies of electronic health records are a crucial element of the US National Institutes of Health's RECOVER Initiative, which is addressing the urgent need to understand long COVID, identify treatments, and accurately identify who has it-the latter is the aim of this study.